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This lesson is part of the following series:

Taught by Professor George Wolfe, this lesson was selected from a broader, comprehensive course, Biology. This course and others are available from Thinkwell, Inc. The full course can be found at http://www.thinkwell.com/student/product/biology. The full course covers evolution, ecology, inorganic and organic chemistry, cell biology, respiration, molecular genetics, photosynthesis, biotechnology, cell reproduction, Mendelian genetics and mutation, population genetics and mutation, animal systems and homeostasis, evolution of life on earth, and plant systems and homeostasis.

George Wolfe brings 30+ years of teaching and curriculum writing experience to Thinkwell Biology. His teaching career started in Zaire, Africa where he taught Biology, Chemistry, Political Economics, and Physical Education in the Peace Corps. Since then, he's taught in the Western NY region, spending the last 20 years in the Rochester City School District where he is the Director of the Loudoun Academy of Science. Besides his teaching career, Mr. Wolfe has also been an Emmy-winning television host, fielding live questions for the PBS/WXXI production of Homework Hotline as well as writing and performing in "Football Physics" segments for the Buffalo Bills and the Discover Channel. His contributions to education have been extensive, serving on multiple advisory boards including the Cornell Institute of Physics Teachers, the Cornell Institute of Biology Teachers and the Harvard-Smithsonian Center for Astrophysics SportSmarts curriculum project. He has authored several publications including "The Nasonia Project", a lab series built around the genetics and behaviors of a parasitic wasp. He has received numerous awards throughout his teaching career including the NSTA Presidential Excellence Award, The National Association of Biology Teachers Outstanding Biology Teacher Award for New York State, The Shell Award for Outstanding Science Educator, and was recently inducted in the National Teaching Hall of Fame.

About this Author

Founded in 1997, Thinkwell has succeeded in creating "next-generation" textbooks that help students learn and teachers teach. Capitalizing on the power of new technology, Thinkwell products prepare students more effectively for their coursework than any printed textbook can. Thinkwell has assembled a group of talented industry professionals who have shaped the company into the leading provider of technology-based textbooks. For more information about Thinkwell, please visit www.thinkwell.com or visit Thinkwell's Video Lesson Store at http://thinkwell.mindbites.com/.

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This lesson has not been reviewed.

So how and what goes wrong? How does it go wrong and what goes wrong when we get cancer? Have you got a year? Because that's about how long it would take me to tell you. It would take me half the year to learn all of the things that could possibly go wrong, because this whole field of cancer research is an unbelievably highly-funded, highly-structured and very, very in-depth field, and we are making enormous amounts of progress in the field of cancer research. We approach it from a lot of different ways. You can approach it from the treatment perspective, which is, which drugs will suppress or kill cancers and which ones won't? Or you can approach it from, what's going on molecularly that causes cancer and can we approach a cure that way? There are a thousand different ways to approach this whole idea of cancer research.
However, as biologists you and I need to talk about what's going on and what kinds of things go wrong when I say a cell has become cancerous or precancerous. And so I want to talk to you about just two examples of things that can happen in a cancer cell. The reason I've chosen these two is because one of them is a proto-oncogene, and the other thing I want to talk to you about is a gene which is a tumor suppresser gene. So we'll take a look at how these two things work and then you can imagine how, if they go wrong, it might cause cancer. And then in the end, I'll pick you up a little bit. Anyway, let's go on. This is really depressing, talking about cancer. Here we go.
I want to talk to you about ras genes, R-A-S. This particular gene is a proto-oncogene and it has a function. Don't forget that proto-oncogenes are not bad guys. These are the good guys. They're the things that cause your cell to work properly. It's when they lose the "proto" part that we get a little bit worried. So this particular gene, this ras gene, is implicated in that at least 30 percent of human cancers worldwide show some kind of mutated or defective ras gene. How does it work? Well, it's part of what we call a signal transduction pathway.
Now, we talked about signal transduction pathways in another part of the course which you can link to if this doesn't become completely clear. But let me generally speak about what a signal tranduction pathway is. It's something like this. If you have a cell and you have a cell membrane, and you want something on the outside to pick up a signal, that signal has to be transduced into the cell. And generally speaking what you want this signal to do is carry a message to produce something. You and I both know that what this message probably is going to be is "produce a protein." Well, where does that signal have to get? Well, the signal somehow has to get to the nucleus of the cell, and then it has to get through the signal--and obviously, this red thing, whatever it was; this factor out here isn't the thing moving through. You have to have a bunch of chemicals signaling each other, and eventually getting to the nucleus and turning on a piece of DNA. And then that DNA in getting turned on has to make RNA. And the RNA has to then leave the nucleus, got to the ribosome and make the protein. And it's this signal transduction pathway that triggers something on the inside of the nuclear envelope to turn DNA on. So as you can well imagine, this is a fairly complex thing. And the ras gene is indeed a member of a signal transduction pathway, and it's an important member.
Let's see what it does. Let's take a look at a normal cell, and I'll draw on the other side a cancer cell with a ras mutation. So here's a normal cell. I'm going to use the same kind of story I did before. Here's the scoop. This particular receptor's job is to pick up a growth factor. And once that is triggered, the ras protein--the protein made by the ras gene--is one of the primary recipients of this signal. And when this ras protein gets activated by the beginning of this signal it starts a message. And it goes through a whole, I'm going to call it, signal transduction pathway--a series of chemicals that, using phosphorylated intermediates--those molecules we know and love--eventually sends a message to the nucleus. And what that nucleus is going to do is, the DNA is going to be triggered to make a protein. And guess what that protein does? That protein stimulates the cell cycle or stimulates cell division. That's a good situation. We have nice controls in there. Growth factor, ras protein, everything is hunky-dory. Unless the gene that makes the ras protein is defective, and then what happens is this. In that situation, we still have our receptor molecule; we still have our ras protein; but guess what? In a cancerous situation, this will stimulate the pathway without the growth factor. And so we're literally circumventing our safety factor. That's going to cause stimulating cell division, which is called cancer because it will happen uncontrollably. It doesn't matter how many growth factors you have, it's uncontrollable. That's cancer.
Let me tell you about tumor suppresser genes. And one I want to tell you about in particular is one called p53. P53, if you've read any kind of cancer research, has gotten an awful lot of publicity. It's implicated that in about 50 percent of human cancers there's a defect in this gene. This is a tumor suppresser gene. What does it do? It suppresses tumors. How does it suppress tumors? Let's take a look. It turns out that we can refer to this as a "guardian angel gene." A lot of people refer to it as that. It's kind of cool. Let's see what it does.
Well, what do genes do? DNA makes RNA; RNA makes protein. So the tumor suppresser gene makes a protein. It turns out that these tumor suppresser proteins end up as not tumor suppressers in themselves but as a transcription factor. Oh, look, it's all tying together! I hope you guys know your molecular biology. It's a transcription factor. What's a transcription factor? Think, think, think. A transcription factor was a protein, a generic protein that was necessary for RNA polymerase to land on the DNA molecule. Without them, RNA polymerase can't work. So this protein made by the tumor suppresser gene is going to be a transcription factor that allows the making of some other proteins.
What do those proteins do? I don't want to get too complicated here, but here's one. This transcription factor will go to one particular gene called gene p21 and allow transcription of a protein--well, of RNA that's eventually going to make a protein. And guess what? This is a brake, as in B-R-A-K-E. It stops the cell cycle. A screeching halt. No more mitosis. Why? Because this protein triggers another transcription and it goes to some other genes which make proteins, and these proteins--so transcription factor, this particular protein that was made by the p53 gene is going to go to another gene to make another protein, and guess what this protein does? It repairs DNA, damaged DNA; for example, DNA damaged by x-rays, DNA damaged by ultraviolet radiation. So look, they're working together. P53 makes a protein that acts as a transcription factor to go to a gene to stop the cell cycle so that it can go to a gene and make proteins to repair the damaged DNA, and then it can turn back on again. But it's also the gene of last resort because it also triggers something called "apoptosis." If your DNA is irreparably damaged and those other two proteins can't work, apoptosis is cell suicide, cell death. In other words, we've got a rotten apple; let's get it out of the barrel. And so it's literally going to make proteins that cause apoptosis.
Now, lest you're horribly depressed and don't want to learn any more biology, let me just finish with this. All in all, it's still pretty tough to get cancer. One of the things we've learned is that in colon cancer you need to have at least six different genes mutated or six different genetic variations, including one oncogene and one tumor suppresser gene not working. So to get colon cancer, which is very, very well defined because we've studied it so much, you've got to have at least six mutations. And here's the other thing we think. We think that environmental things go into this, too. So we say, "this causes cancer." It looks like, quite often, the environmental elements are going to trigger some of these changes that cause cancer.
Then I want to add one last thing to tie this all together. Why are cancer cells immortal? Remember telomeres? If you don't know anything about telomeres, you may want to listen about telomeres. There's an enzyme called telomerase. Telomerase catalyzes the formation of telomeres. What are telomeres? Telomeres are the ends of chromosomes that gradually wear down and eventually get to the point where the chromosomes can no longer replicate. But if you're remaking those ends, think about it: you have chromosomes that can constantly replicate.
You know, the interesting thing about all of this is it explains cancer in a way that is so clear why tendencies to cancers run in families, and why chemotherapeutic agents can work, because sometimes they can destroy the products of the genes or enhance the products of the genes. I hope some of you bright individuals go into cancer research because, you know what? We're this close.
Cell Reproduction
Regulating Mitosis
The Ras Gene and the p53 Gene Page [1 of 2]

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